Duran Amanda M, Meiler Jens
Center for Structural Biology, Department of Chemistry, Vanderbilt University, Nashville, TN 37212, USA.
Comput Struct Biotechnol J. 2013 Nov 9;8:e201308004. doi: 10.5936/csbj.201308004. eCollection 2013.
Helical membrane proteins such as transporters, receptors, or channels often exhibit structural symmetry. Symmetry is perfect in homo-oligomers consisting of two or more copies of the same protein chain. Intriguingly, in single chain membrane proteins, often internal pseudo-symmetry is observed, in particular in transporters and channels. In several cases single chain proteins with pseudo-symmetry exist, that share the fold with homo-oligomers suggesting evolutionary pathways that involve gene duplication and fusion. It has been hypothesized that such evolutionary pathways allow for the rapid development of large proteins with novel functionality. At the same time symmetry can be leveraged to recognize highly symmetric substrates such as ions. Here we review helical transporter proteins with an inverted two-fold pseudo-symmetry. In this special scenario the symmetry axis lies in the membrane plane. As a result, the putative ancestral monomeric protein would insert in both directions into the membrane and its open-to-the-inside and open-to-the-outside conformations would be structurally identical and iso-energetic, giving a possible evolutionary pathway to create a transporter protein that needs to flip between the two states.
诸如转运蛋白、受体或通道之类的螺旋膜蛋白常常呈现出结构对称性。在由两条或更多条相同蛋白质链的拷贝组成的同型寡聚体中，对称性是完美的。有趣的是，在单链膜蛋白中，常常能观察到内部假对称性，尤其是在转运蛋白和通道中。在一些情况下，存在具有假对称性的单链蛋白，它们与同型寡聚体具有相同的折叠方式，这暗示了涉及基因复制和融合的进化途径。据推测，这样的进化途径能够使具有新功能的大蛋白快速发展。同时，对称性可被用于识别高度对称的底物，如离子。在此，我们综述具有反向二重假对称性的螺旋转运蛋白。在这种特殊情况下，对称轴位于膜平面内。因此，推测的祖先单体蛋白会在两个方向上插入膜中，并且其向内开放和向外开放的构象在结构上是相同的且能量相等，这为创建一种需要在两种状态之间翻转的转运蛋白提供了一种可能的进化途径。
